Byssinosis is a significant cause of pulmonary problems among cotton mill workers. The typical symptoms of shortness of breath, chest tightness, and wheezing usually occur several hours after the beginning of the work shift, particularly after a week-end away from the mill; this characteristic temporal profile distinguishes byssinosis from other pulmonary occupational exposure syndromes. Byssinotic workers may progress to develop severe pulmonary disability even after exposure has ceased. The causitive agent or agents appear to be found in the cotton bract, the samll leaves immediately below the boll. This proposal will investigate on a cellular level the toxicity of condensed tannin, a component of the bract, on porcine endothelial cells derived from the thoracic aorta and pulmonary artery. The endothelial cell is appropriate for these studies because the endothelial bed of the lung is in close proximity to the airway, and is exposed to inhaled agents that diffuse past the cells lining the air spaces. For comparison, porcine skin fibroblasts will be studied as control cells unlikely to be exposed to tannin in vivo. We will measure direct cellular toxicity using assays of 51Cr release and lactate dehydrogenase release. Sublethal cellular injury will be studied by measuring the effect of tanning exposure on protein systhesis, pinobytotic rate, surface protein expression, and uptake of 5-hydroxytryptamine. In addition, the effect of tannin exposure on endothelial cell-platelet interactions will be evaluated. The results obtained with purified tannin will be compared to those observed with crude bract extract to assess the contribution of tannin to bract-mediated toxic effects. We believe that our possession of purified tannin and homogeneous cell culture systems will allow us to define better the toxic potential of the cotton bract than has been possible before.